Cholesteryl hemisuccinate (CHS)-conjugated chitosan (CS)-based self-assembled nanoparticles (NPs) were developed for enhancing the intracellular uptake of docetaxel in multidrug resistance (MDR)-acquired cancer cells. CHS-CS was successfully synthesized and self-aggregation, particle size, zeta potential, drug entrapment efficiency, and in vitro drug release of docetaxel-loaded CHS-CS NPs were tested. The optimized NPs had a mean hydrodynamic diameter of 303 nm, positive zeta potential of 21.3 mV, and spherical shape. The in vitro release of docetaxel from the optimized CHS-CS NPs in different pH medium (pH 6.0 and 7.4) revealed that the release was improved in a more acidic condition (pH 6.0), representing a tumor cell's environment. The superior MDR-overcoming effect of docetaxel-loaded CHS-CS NPs, compared with docetaxel solution, was verified in anti-proliferation and cellular accumulation studies in MDR-acquired KBV20C cells. Thus, CHS-CS NPs could be potentially used for overcoming the MDR effect in anticancer drug delivery.
Keywords: chitosan; cholesterol; docetaxel; multidrug resistance-overcoming; nanoparticles.